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Nitric Oxide Releasing Solutions to Prevent and Treat Mild/Moderate COVID-19 Infection (NOCOVID)

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ClinicalTrials.gov Identifier: NCT04337918
Recruitment Status : Completed
First Posted : April 8, 2020
Last Update Posted : February 10, 2021
Sponsor:
Collaborators:
The Emmes Company, LLC
Keyrus Life Science
Information provided by (Responsible Party):
Sanotize Research and Development corp.

Tracking Information
First Submitted Date  ICMJE April 6, 2020
First Posted Date  ICMJE April 8, 2020
Last Update Posted Date February 10, 2021
Actual Study Start Date  ICMJE May 8, 2020
Actual Primary Completion Date January 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
  • Prevention Study: Measure the effect of NORS on the prevention of COVID-19 infection among health care professionals at risk of exposure to COVID-19 [ Time Frame: 14 days ]
    Measure the proportion of subjects with either swab positive COVID-19 or presentation of clinical symptoms as measured by fatigue with either fever >37.2 (oral)and/or a persistent cough.
  • Treatment Sub Study: Measure the efficacy of NORS at reducing the progression of COVID- 19 [ Time Frame: 21 days ]
    Measure the proportion of participants requiring requiring hospitalization for COVID-19/flu-like symptoms and/or needing oxygen therapy, BIPAP/CPAP, intubation and mechanical ventilation following enrollment.
Original Primary Outcome Measures  ICMJE
 (submitted: April 6, 2020)
  • Prevention Primary Endpoint [ Time Frame: 21 days ]
    To assess the efficacy of NORS in prevention of COVID-19 infection among health care professionals at risk of exposure to COVID-19. Proportion of subjects with either positive COVID-19 or presentation of clinical symptoms defined as fatigue with either fever >37.2 (oral) and/or a persistent cough in NORS vs control group by 21 days following randomization.
  • Treatment Sub Study Primary Endpoint [ Time Frame: 28 days ]
    To assess the efficacy of NORS in prevention of progression of COVID- 19. Proportion of participants requiring respiratory support defined as oxygen therapy, BIPAP/CPAP, intubation and mechanical ventilation by 28 days following enrollment. Proportion of participants requiring hospitalization for COVID-19/flu-like symptoms by 28 days following enrollment.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
  • Prevention Study: Measure the effect of NORS on the prevention of progression of COVID- 19 [ Time Frame: 21 days ]
    Measure the proportion of participants requiring requiring hospitalization for COVID-19/flu-like symptoms and/or needing oxygen therapy, BIPAP/CPAP, intubation and mechanical ventilation following enrollment.
  • Prevention Study: Measure the tolerability of NORS treatments [ Time Frame: 21 days ]
    Measure the tolerability of the NORS treatments as determined by number of adverse events, pain, discomfort or discontinuations of treatment.
  • Treatment Sub Study: Measure the virucidal effect of NORS Treatments [ Time Frame: 21 days ]
    Measure the median number of days to negative conversion of SARS-CoV-2 RT-PCR from a nasopharyngeal swabs.
  • Treatment Sub Study: Determine effect of NORS on the speed of clinical recovery [ Time Frame: 21 days ]
    Determine the time to clinical recovery in participants with COVID-19 by measuring the median number of days from enrollment to discharge (if admitted), or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air).
  • Treatment Sub Study: Determine the reduction in clinical symptoms [ Time Frame: 21 days ]
    Measure the reduction clinical symptoms in participants with COVID- 19 by the magnitude of the change in Modified Jackson Cold Score Diary Score (5-unit change is a substantial clinical benefit).
  • Treatment & Sub Study: Determine positive sero-conversion for SARS-CoV-2 [ Time Frame: 21 days ]
    Measure the proportion of participants that have a positive sero-conversion for SARS-CoV-2
Original Secondary Outcome Measures  ICMJE
 (submitted: April 6, 2020)
  • Prevention Secondary Endpoint [ Time Frame: 28 days ]
    To assess the efficacy of NORS in prevention of progression of COVID- 19. Proportion of participants requiring respiratory support defined as oxygen therapy, BIPAP/CPAP, intubation and mechanical ventilation in NORS vs control group by 28 days following randomization. Proportion of participants requiring hospitalization for COVID-19/flu-like symptoms in NORS vs control group by 28 days following randomization.
  • Prevention Secondary Endpoint [ Time Frame: 28 days ]
    To assess the tolerability of the NORS treatments. Adverse events, pain, discomfort or discontinuations of treatment.
  • Treatment Sub Study Secondary Endpoint [ Time Frame: 28 days ]
    To assess the virucidal effect of NORS in participants with COVID-19. Median number of days to negative conversion of SARS-CoV-2 RT-PCR from an oropharyngeal or a nasopharyngeal swab with follow-up through 28 days from enrollment.
  • Treatment Sub Study Secondary Endpoint [ Time Frame: 28 days ]
    To assess NORS efficacy on time to clinical recovery in participants with COVID-19. Median number of days from enrollment to clinical recovery with follow-up through 28 days. Clinical recovery defined as discharge (if admitted), or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air).
  • Treatment Sub Study Secondary Endpoint [ Time Frame: 28 days ]
    To assess reduction of clinical symptoms in participants with COVID- 19. Change in Modified Jackson Cold Score Diary Score.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nitric Oxide Releasing Solutions to Prevent and Treat Mild/Moderate COVID-19 Infection
Official Title  ICMJE Multi-Center, Randomized, Controlled, Phase II Clinical Efficacy Study Evaluating Nitric Oxide Releasing Solution Treatment for the Prevention and Treatment of COVID-19 in Healthcare Workers and Individuals at Risk of Infection
Brief Summary This is a multi-center, randomized, controlled, phase II clinical efficacy study evaluating a novel Nitric Oxide Releasing Solution (NORS) treatment for the prevention and treatment of COVID-19 in healthcare workers at risk of infection. Participants will be enrolled into one of two components of this study. Based on initial swabs/symptoms, volunteers who are COVID-19 negative will be enrolled in the Prevention study and randomized to receive standard institutional precautions or standard institutional precautions + NORS. Those who are COVID-19 positive will be enrolled in the open-label Treatment Sub-Study.
Detailed Description

The novel, human-infecting corona-virus, provisionally named 2019 novel corona virus (2019-nCoV) is a single-strand, positive-sense RNA virus and has a similar receptor-binding domain structure to that of SARS-CoV and MERS-CoV. The virus is transmitted via airborne droplets to the nasal mucosa. Replication occurs locally in the nasal mucosa, in ciliated epithelial cells, over a 3-day incubation period. The mucosal cells are damaged with a resultant inflammatory response similar to the common cold. During this time the virus is shed in nasal secretions causing disease in the lower respiratory tract, potentially causing fatal viral pneumonia.

The literature supports that NO or its derivatives have inhibitory effects on a variety of viral infections. This inhibitory effect was shown to be marked in Interferon (IFN) mediated inhibition manifested by activated macrophage. It was also shown to be correlated with s-nitrosylation of viral proteins such as reductases and proteases.

Based on the genetic similarities between SARS and corona viruses, similar viricidal effects of NO on COVID-19 can be hypothesized.

SaNOtize has developed an innovative approach to provide nitric oxide gas using a formulation called Nitric Oxide Releasing Solution (NORS). This patented solution releases virucidal doses of NO for a sustained period and is effective at rapidly inactivating Influenza A and SARS-CoV-2.

NORS delivered as a gargle (AM), nasal spray (PRN) or as a nasopharyngeal flush (PM) has the potential to decontaminate the upper respiratory tract that could preventing transmission and progression of COVID-19 in Healthcare Workers & Individuals at Risk of Infection.

The randomized Prevention study will investigate the ability of NORS to prevent COVID-19 infection when used prophylactically. The open-label Treatment Sub-Study is expected to be small and will provide pilot data on the possibility of NORS as a treatment for Mild/Moderate COVID-19 infection.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Multi-center, prospective, randomized, controlled, phase II, parallel group
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Corona Virus Infection
Intervention  ICMJE
  • Drug: NORS (Nitric Oxide Releasing Solution)
    NORS treatment will consist of daily self-administration of three routes; Nitric Oxide Gargle (NOG) every morning, Nitric Oxide Nasophyaryngeal Irrigation (NONI) every evening, and Nitric Oxide Nasal Spray (NONS) up to 5 times per day.
    Other Name: NOG, NONI, NONS
  • Drug: NORS (Nitric Oxide Releasing Solution)

    Up to ten volunteers who are found to be COVID-19 positive during screening will be eligible to enroll in the 21-day Treatment sub-study and receive daily NORS treatment for 14 days. NORS treatment will consist of daily self-administration of three routes; Nitric Oxide Gargle (NOG) every morning, Nitric Oxide Nasophyaryngeal Irrigation (NONI) every evening, and Nitric Oxide Nasal Spray (NONS) up to 5 times per day.

    Any participants enrolled in the Prevention study who meet the criteria for the sub study will roll over into the Treatment Sub-Study but must remain in their randomly assigned group.

    Other Name: NOG, NONI, NONS
Study Arms  ICMJE
  • No Intervention: Prevention - Standard Precautions
    Participants COVID-19 negative at baseline will be randomized to receive standard COVID-19 screening and protection (per their facility or organization's protocols).
  • Experimental: Prevention - NORS + Standard Precautions
    Participants COVID-19 negative at baseline will be randomized to receive standard COVID-19 screening and protection (per their facility or organization's protocols) plus daily NORS treatment for 14 days.
    Intervention: Drug: NORS (Nitric Oxide Releasing Solution)
  • Treatment Sub-Study

    Volunteers who are found to be COVID-19 positive during screening will be eligible to enroll in the 21-day Treatment sub-study and receive daily NORS treatment for 14 days. Ten participants can be directly enrolled in the Treatment sub-study.

    Participants enrolled in the Prevention study who meet the criteria in this section will roll over into the Treatment Sub-Study but must remain in their randomly assigned group.

    Intervention: Drug: NORS (Nitric Oxide Releasing Solution)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 7, 2021)
143
Original Estimated Enrollment  ICMJE
 (submitted: April 6, 2020)
200
Actual Study Completion Date  ICMJE February 2, 2021
Actual Primary Completion Date January 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Prevention Study Inclusion Criteria:

  1. Capable of understanding and providing signed informed consent and ability to adhere to the requirements and restrictions of this protocol;
  2. Men and Women ≥ 19 years of age unless local laws dictate otherwise;
  3. English speaking;
  4. Must be willing to use an adequate form of contraception (or abstinence) from the time of the first dose with the IMP until after the last dose of IMP.
  5. Be symptom-free at screening/baseline.
  6. Work/live in contact with COVID-19 infected patients or scheduled to work in a setting with high likelihood of contact with COVID-19 infected patients.

Prevention Study Exclusion Criteria:

  1. Prior Tracheostomy;
  2. Concomitant treatment of respiratory support (involving any form of oxygen therapy);
  3. Any clinical contraindications, as judged by the attending physician;
  4. Any symptoms consistent with COVID-19;
  5. Pregnant;
  6. Mentally or neurologically disabled patients who are considered not fit to consent to their participation in the study;
  7. Prior COVID-19 infection.

Treatment Sub study Inclusion Criteria:

  1. Capable of understanding and providing signed informed consent and ability to adhere to the requirements and restrictions of this protocol;
  2. Men and Women ≥ 19 years of age unless local laws dictate otherwise;
  3. English speaking;
  4. Must be willing to use an adequate form of contraception (or abstinence) from the time of the first dose with the IMP until after the last dose of IMP;
  5. Positive COVID-19 test or presentation of clinical symptoms defined as fatigue with either fever >37.2 (oral) and/or a persistent cough.

Treatment Sub Study Exclusion Criteria:

  1. Prior Tracheostomy;
  2. Concomitant treatment of respiratory support (involving any form of oxygen therapy); Any clinical contraindications, as judged by the attending physician;
  3. Mentally or neurologically disabled patients who are considered not fit to consent to their participation in the study;
  4. Pregnant;
  5. Currently hospitalized for symptoms of COVID-19.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04337918
Other Study ID Numbers  ICMJE COVID-CTP-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sanotize Research and Development corp.
Study Sponsor  ICMJE Sanotize Research and Development corp.
Collaborators  ICMJE
  • The Emmes Company, LLC
  • Keyrus Life Science
Investigators  ICMJE
Principal Investigator: Jeremy Road, MD Private Practice
PRS Account Sanotize Research and Development corp.
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP